The proposed Pacific Northwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research (PNWRCE) brings together a consortium of investigators with extensive expertise and basic and translational research capacity directed at a broad range of NIAID Category A-C Priority Pathogens. Our research activities are aimed at providing a deeper understanding of pathogen-host interactions;how these interactions impact innate and adaptive immune responses;and the age-related defects in immunity that lead to immunosenescence and an increased vulnerability to infectious disease. The information generated from these activities will facilitate the development of next-generation therapeutics, diagnostics, and vaccines against Category A-C Pathogens. The PNWRCE will also train young investigators for biodefense and emerging infectious disease research, foster the development of new research programs, and provide facilities and scientific support to first-line responders in the event of a national biodefense or emerging infectious disease emergency. RESEARCH THEMES The research activities of the PNWRCE are unified by two distinct but interrelated themes: The identification of age-related defects in the immune system to facilitate the development of vaccines and supplemental therapies and The use of systems biology and systems genetics approaches to define pathogen-host interactions and mechanisms of innate and adaptive immunity These themes reflect the strengths of PNWRCE investigators and are geared toward addressing significant public health needs and gaps in the current RCE program. In particular, our use of systems-level approaches and our focus on innate and adaptive immunity and immunosenescence provide new opportunities to identify targets for therapeutic intervention and enhancements to current vaccine strategies. Moreover, our research activities are designed to extend these benefits to vulnerable populations, including the aged, which represents the fastest growing segment of American society. Our focus on the host side of pathogen-host interactions will allow us to discover new cellular targets for antiviral products that are less likely to be sensitive to escape through pathogen mutation and more likely to have a broad spectrum of action. As outlined in the NIAID Strategic Plan for Biodefense Research (2007 Update), the development of broad-spectrum drugs, particularly antivirals, is an NIAID priority. The development of broad-spectrum platforms is also encouraged, and we will generate and make available an innovative mouse systems genetics platform that can be used to identify host susceptibility alleles to a variety of pathogens. The broad-spectrum strategy recognizes the expanding range of biological threats and the need for a more responsive biodefense capability. In this regard, there is a pressing need for vaccines against many Category A-C Pathogens, and our research will enhance vaccine development strategies as well as provide new methods for the early evaluation of vaccine efficacy through the identification of genomic correlates of immunity.